Involvement of a mitochondrial phosphatase in the regulation of ATP production and insulin secretion in pancreatic β cells

被引:128
作者
Pagliarini, DJ
Wiley, SE
Kimple, ME
Dixon, JR
Kelly, P
Worby, CA
Casey, PJ
Dixon, JE [1 ]
机构
[1] Univ Calif San Diego, Dept Pharmacol Cellular & Mol Med, La Jolla, CA 92093 USA
[2] Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA
[3] Univ Calif San Diego, Biomed Sci Grad Program, La Jolla, CA 92093 USA
[4] Duke Univ, Med Ctr, Dept Pharmacol, Durham, NC 27710 USA
关键词
D O I
10.1016/j.molcel.2005.06.008
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Reversible phosphorylation is the cell's most prevalent form of posttranslational modification, yet its role in the regulation of mitochondrial functions is poorly understood. We have discovered that a member of the dual-specific protein tyrosine phosphatase (DS-PTP) family, PTPMT1 (PTP localized to the Mitochondrion 1) resides nearly exclusively in mitochondria. PTPMT1 is targeted to the mitochondrion by an N-terminal signal sequence and is found anchored to the matrix face of the inner membrane. Knockdown of PTPMT1 expression in the pancreatic insulinoma cell line INS-1 832/ 13 alters the mitochondrial phosphoprotein profile and markedly enhances both ATP production and insulin secretion. These data define PTPMT1 as a potential drug target for the treatment of type II diabetes and strengthen the notion that mitochondria are an underappreciated site of signaling by reversible phosphorylation.
引用
收藏
页码:197 / 207
页数:11
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